AJP - Heart and Circulatory Physiology, Vol 251, Issue 3 601-H611, Copyright © 1986 by American Physiological Society
Carbachol inhibits electrophysiological effects of cyclic AMP in ventricular myocytes
D. P. Rardon and A. J. Pappano
Muscarinic agonists inhibit beta-adrenoceptor-mediated electrophysiological
effects in mammalian cardiac ventricular tissues. However, the site or
sites of interaction are not entirely clarified. To address this problem,
the effect of carbachol on isoproterenol-, 3-isobutyl-1-methylxanthine-,
and forskolin-induced action potential changes was examined in guinea pig
ventricular myocytes. Following enzymatic dispersion, myocytes had a
resting membrane potential of -81.3 +/- 3 mV in 5.4 mM K+ Tyrode solution,
and stimulated action potentials were 348 +/- 17 ms in duration (n = 17).
Elevated extracellular [K+] ([K+]o) depolarized the membrane 56.5 mV per
10-fold increase in [K+]o. The estimated intracellular K+ activity was
115.7 mM. Carbachol (10(-6) M) alone produced no electrophysiological
changes but antagonized isoproterenol-, 3-isobutyl-1-methylxanthine-, and
forskolin-induced action potential prolongation by 84 +/- 11, 88 +/- 17,
and 83 +/- 14%, respectively. Transient depolarizations produced in
isoproterenol (10(-8) M), 3-isobutyl-1-methylxanthine (10(-5) M), and
forskolin (10(-7) M), but not those produced in ouabain (10(-6) M), were
antagonized by carbachol (10(-6) M). These data show that enzymatically
dispersed myocytes maintain pharmacological and electrophysiological
properties similar to those of cells in tissues, carbachol antagonizes
electrophysiological effects of isoproterenol, 3-isobutyl-1-methylxanthine,
and forskolin, and carbachol inhibits cyclic AMP-mediated effects at a site
or sites in the cyclic AMP cascade distal to the catalytic unit of
adenylate cyclase.
